Gabapentin-mediated inhibition of voltage-activated Ca2+ channel currents in cultured sensory neurones is dependent on culture conditions and channel subunit expression

Martin, Duncan J.; McClelland, David; Herd, Murray B.; Sutton, Kathy G.; Hall, Matthew D.; Lee, K; Pinnock, R.D.; Scott, Roderick H.

doi:10.1016/s0028-3908(01)00181-2

Cited by 133 publications

(101 citation statements)

References 19 publications

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“…Interestingly, protein kinase C activation has been shown to lead to an increased insertion of calcium channels of the Ca v 2 family at the plasma membrane (Zhang et al, 2008). This also reflects previous experimental findings that the observation of effects of GBP in vitro depends on culture conditions (Alden and García, 2001;Martin et al, 2002).…”

Section: Discussionsupporting

confidence: 77%

The α₂δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α₂δ-2

Tran-Van-Minh¹,

Dolphin²

2010

J. Neurosci.

134

135

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The ␣ 2 ␦ subunits of voltage-gated calcium channels are important modulatory subunits that enhance calcium currents and may also have other roles in synaptogenesis. The antiepileptic and antiallodynic drug gabapentin (GBP) binds to the ␣ 2 ␦-1 and ␣ 2 ␦-2 isoforms of this protein, and its binding may disrupt the binding of an endogenous ligand, required for their correct function. We have shown previously that GBP produces a chronic inhibitory effect on calcium currents by causing a reduction in the total number of ␣ 2 ␦ and ␣ 1 subunits at the cell surface. This action of GBP is likely to be attributable to a disruption of the trafficking of ␣ 2 ␦ subunits, either to or from the plasma membrane. We studied the effect of GBP on the internalization of, and insertion into the plasma membrane of ␣ 2 ␦-2 using an ␣-bungarotoxin binding site-tagged ␣ 2 ␦-2 subunit, and a fluorescent derivative of ␣-bungarotoxin. We found that GBP specifically disrupts the insertion of ␣ 2 ␦-2 from post-Golgi compartments to the plasma membrane, and this effect was prevented by a mutation of ␣ 2 ␦-2 that abolishes its binding to GBP. The coexpression of the GDP-bound Rab11 S25N mutant prevented the GBP-induced decrease in ␣ 2 ␦-2 cell surface levels, both in cell lines and in primary neurons, and the GBP-induced reduction in calcium channel currents. In contrast, the internalization of ␣ 2 ␦-2 was unaffected by GBP. We conclude that GBP acts by preventing the recycling of ␣ 2 ␦-2 from Rab11-positive recycling endosomes to the plasma membrane.

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Section: Discussionsupporting

confidence: 77%

The α₂δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α₂δ-2

Tran-Van-Minh¹,

Dolphin²

2010

J. Neurosci.

134

135

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“…To obtain cDNA, 200 ng total RNA was reverse-transcribed with use of the Taqman Gold reverse transcription-polymerase chain reaction (RT-PCR) kit (Applied Biosystems). Real-time PCR analysis was done with an iCycler iQ detection system (Bio-Rad) in a master mix that contained specific primers, as described elsewhere (400 nmol/L for Ca v 1.2 21 and cyclophilin 22 ; 500 nmol/L for K v 4.2 23 ), AmpliTaq Gold DNA polymerase, and Taqman probes (100 nmol/L) tagged at the 5Ј end with the fluorescent molecule 6-carboxyfluorescein (5Ј-FAM) containing the fluorescent quencher moiety 6-carboxytetramethylrhodamine (3Ј-TAMRA) in 3Ј. Each measurement was performed in triplicate.…”

Section: Cell Isolation and Recording Techniquesmentioning

confidence: 99%

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

et al. 2004

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Background-Cardiac hypertrophy underlies arrhythmias and sudden death, for which mineralocorticoid receptor (MR) activity has recently been implicated. We sought to establish the sequence of ionic events that link the initiating insult and MR to hypertrophy development. Methods and Results-Using whole-cell, patch-clamp and quantitative reverse transcription-polymerase chain reaction techniques on right ventricular myocytes of a myocardial infarction (MI) rat model, we examined the cellular response over time. One week after MI, no sign of cellular hypertrophy was found, but action potential duration (APD) was lengthened. Both an increase in Ca 2ϩ current (I Ca ) and a decrease in K ϩ transient outward current (I to ) underlay this effect. Consistently, the relative expression of mRNA coding for the Ca 2ϩ channel ␣1C subunit (Ca v 1.2) increased, and that of the K ϩ channel K v 4.2 subunit decreased. Three weeks after MI, AP prolongation endured, whereas cellular hypertrophy developed. I Ca density, Ca v 1.2, and K v 4.2 mRNA levels regained control levels, but I to density remained reduced. Long-term treatment with RU28318, an MR antagonist, prevented this electrical remodeling. In a different etiologic model of abdominal aortic constriction, we confirmed that APD prolongation and modifications of ionic currents precede cellular hypertrophy. Conclusions-Electrical remodeling, which is triggered at least in part by MR activation, is an initial, early cellular response to hypertrophic insults.

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“…Numerous studies have examined the effects of gabapentin or pregabalin on voltage-gated calcium channel function. There are several reports that the drugs reduce calcium current in neuronal cell body membranes (Stefani et al, 1998;Martin et al, 2003;McClelland et al, 2004). However, in other studies with neurons (van Hooft et al, 2002) or recombinant systems (Canti et al, 2003), gabapentin was inactive.…”

mentioning

confidence: 99%

New horizons in the development of antiepileptic drugs: Innovative strategies

Löscher¹,

Schmidt²

2006

Epilepsy Research

104

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Gabapentin-mediated inhibition of voltage-activated Ca2+ channel currents in cultured sensory neurones is dependent on culture conditions and channel subunit expression

Cited by 133 publications

References 19 publications

The α₂δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α₂δ-2

The α₂δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α₂δ-2

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

New horizons in the development of antiepileptic drugs: Innovative strategies

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Gabapentin-mediated inhibition of voltage-activated Ca2+ channel currents in cultured sensory neurones is dependent on culture conditions and channel subunit expression

Cited by 133 publications

References 19 publications

The α2δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α2δ-2

The α2δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α2δ-2

Mineralocorticoid Receptor Antagonism Prevents the Electrical Remodeling That Precedes Cellular Hypertrophy After Myocardial Infarction

New horizons in the development of antiepileptic drugs: Innovative strategies

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Resources

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The α₂δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α₂δ-2

The α₂δ Ligand Gabapentin Inhibits the Rab11-Dependent Recycling of the Calcium Channel Subunit α₂δ-2